title: Increased EZH2 protein expression is associated with invasive urothelial carcinoma of the bladder.
abstract: OBJECTIVE
  Elevated polycomb group protein Enhancer of Zest Homolog 2 (EZH2) expression has been associated with progression to more advanced disease in a variety of malignancies. We examined EZH2 protein expression levels in bladder tissue specimens from patients with urothelial carcinoma (UC) and investigated the relationship between EZH2 protein expression and clinical outcomes.
  
  
  METHODS
  Tissue microarrays (TMAs) were constructed using bladder tissue specimens from radical cystectomies performed for UC at our institution between 1994 and 2002. EZH2 expression was measured by immunohistochemistry and scoring was based on percentage and intensity of positive nuclear staining. A receiver operating curve (ROC) was generated to differentiate cancerous from benign lesions using EZH2 protein scores. Recurrence-free survival was estimated using the Kaplan-Meier approach with log-rank test. A multivariate Cox proportional hazards model was used to assess independent contributions.
  
  
  RESULTS
  A total of 454 TMA specimen spots from 81 patients were evaluated. EZH2 protein levels in invasive high grade UC were significantly elevated compared with adjacent benign urothelium, noninvasive low grade UC, and CIS. EZH2 protein levels were also significantly increased in CIS and noninvasive low grade UC compared with adjacent benign urothelium. We found no association between EZH2 protein expression and clinical outcomes following radical cystectomy in our cohort of patients.
  
  
  CONCLUSIONS
  EZH2 overexpression is a common event in UC of the bladder. Elevated EZH2 protein levels are associated with more aggressive bladder cancer, including invasive UC. EZH2 may therefore serve as a useful biomarker for UC.
authors.affiliation: Department of Urology, James Buchanan Brady Urological Institute, Baltimore, MD 21287, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Wang
authors.forename: Roula
authors.initials: R
authors.lastname: Albadine
authors.forename: Ahmed
authors.initials: A
authors.lastname: Magheli
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Guzzo
authors.forename: Mark W
authors.initials: MW
authors.lastname: Ball
authors.forename: Stefan
authors.initials: S
authors.lastname: Hinz
authors.forename: Mark P
authors.initials: MP
authors.lastname: Schoenberg
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
authors.forename: Mark L
authors.initials: ML
authors.lastname: Gonzalgo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015653:Cystectomy / Q000379:methods; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D063151:Polycomb Repressive Complex 2 / Q000096:biosynthesis*; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis / Q000706:statistics & numerical data; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2